Continued support is requested for a hypertension research program based on identifying and typing heterogeneity among hypertensive patients using endocrine profiles related to electrolyte metabolism. These profiles are applied to analysis of associated clinical and physiologic characteristics for understanding causal mechanisms and for development of new and more specific treatments. Recent developments make it possible to subclassify the "essential" hypertension population on the basis of definable abnormalities in the renin-angiotensin-aldosterone system, separating patients first in terms of abnormalities in renin secretion and then subdividing them according to variations in secretion of adrenal cortical steroids. Basically our approach is to apply information gleaned from detailed metabolic ward studies to out-patients. The out-patient center in turn is a source of characterized patients for more detailed in-patient study. Using hormonal profiling, longitudinal analysis has suggested differences in mechanisms, clinical course and prognosis in patients with essential hypertension. These suggestions will be pursued prospectively with larger numbers. Also, our experience indicates that in exposing hormonal deviations among the endocrine subgroups derived from the initial renin-sodium index it is then possible to develop new simpler treatments directed specifically against the hormonal deviation, or the lesion to which it points. Within the renin subgroups, clearer definition of heterogenity will be accomplished by indepth association of endocrine profiles with physiological, hemodynamic and pharmacologic characteristics. Attention will be given to volume/vasoconstrictor and related mechanisms in those subgroups refractory to treatment. The program will be expanded to pediatric patients and industrial population and to include nephric and anephric patients with end-stage kidney disease. Clinical studies will be supported by new biochemical studies of renin system components, and of autonomic and other steroid hormones. Parallel studies in animal models and of other relevant human disorders will serve to validate the clinical findings. Computer systems will be used for data collection and analysis and also to test our model of hormonal and circulatory behavior which is used as the conceptual focus.